Do medical devices contribute to sustainability? The role of innovative polymers and device design.

Sustainability of a medical device has not yet become a major issue in public discussions compared to other topics with impact to material performance, clinical application, production economy and environmental pollution. Due to their unique properties, polymers (plastics) allow for multiple, flexible applications in medical device technology. Polymers are part of the majority of disposable and single use medical device and contribute with 3% to the worldwide production of plastics. The global medical polymer market size was valued 19.9 billion US-$ in 2022 and its value projection for 2023 is expected to reach 43.03 billion US-$ Here, a wider concept of related sustainability is introduced for medical devices and their polymer components. A close look on medical device specification reveals that additional properties are required to provide sustainability, such as biodegradability, quality by device design (QbD), as well as an inbuild performance service for patients, healthcare professionals and healthcare providers. The increasing global numbers for chronic and non-communicable diseases require a huge demand for single use medical devices. A careful look at polymer specification and its performance properties is needed, including possible chemical modifications and degradation processes during waste disposal. Bioengineers in charge of design and production of medical devices will only be successful when they apply a holistic and interdisciplinary approach to medical device sustainability.

Do medical devices contribute to sustainability? Environmental, societal and governance aspects.

Sustainability of a product or device is currently primarily related to its environmental footprint. Here, a wider concept of sustainability is introduced for medical devices and their components in healthcare provision. Such devices sustain healthcare and patient wellbeing due to their quality specifications for material composition, product design and performance. The term quality must be intended in the most comprehensive term, including purity and biocompatibility of materials, device reliability, limited number of recalls and reduced risks as well as acceptability for patients. A close look on medical device specification shows, however, that additional parameters, such as societal, demographic and economic factors also determine medical device sustainability. The medical device life cycle, from design phase, production process to clinical application and the final disposal, also determines its impact. Recommendations for healthcare operators and managers will complete the hypothesis of this paper, that a thoroughly outlined device choice and operation together with a careful waste management of spent medical devices and their components positively affects medical device sustainability. As an example, the limited quantity of wastes and the reduced risks for adverse reaction have a positive impact on both the environmental pollution and on the costs sustained by the healthcare organisations and by the community. These factors determine both, the success of healthcare manoeuvres and the related environmental footprint.

Contrast-Enhanced Ultrasonography as a Novel Method for the Dynamic Visualization of Blood Flow and Fiber Blockage in Dialyzers: A Feasibility Study.

The capillary dialyzer represents the central element of the extracorporeal blood circuit of a therapy system for hemodialysis. The aim of this study was to assess the blood-flow characteristics of dialyzers with the help of modern ultrasound techniques. Five brand-new dialyzers (FX80 classix, Fresenius Medical Care, Bad Homburg, Germany) and five dialyzers after a dialysis session were analyzed by different ultrasound techniques to detect functional and structural changes. B-mode and Doppler techniques were not suitable to describe differences in brand-new and clinically applied dialyzers. Contrast-enhanced ultrasonography, however, was able to visualize blood-flow profiles in the capillaries. Although dialyzers displayed no signs of clinical dysfunction, contrast-enhanced ultrasonography was able to detect blocked capillaries of varying degrees after a dialysis session in all five examined dialyzers. Consequently, the blood-flow velocity was higher in the remaining unblocked capillaries in comparison to the velocity in the brand-new dialyzers. This information may be helpful for improving the geometric design of dialyzers, including their capillary membranes, and optimizing anti-coagulation strategies in hemodialysis patients.

Hemodiafiltration to Address Unmet Medical Needs ESKD Patients.

Hemodiafiltration combines diffusive and convective solute removal in a single therapy by ultrafiltering 20% or more of the blood volume processed using a high-flux hemodialyzer and maintaining fluid balance by infusing sterile nonpyrogenic replacement fluid directly into the patient's blood. In online hemodiafiltration, the large volumes of replacement fluid required are obtained by online filtration of standard dialysate through a series of bacteria- and endotoxin-retaining filters. Currently available systems for online hemodiafiltration are on the basis of conventional dialysis machines with added features to safely prepare and infuse replacement fluid and closely control fluid balance. Hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis, and recently completed randomized, controlled clinical trials suggest better patient survival with online hemodiafiltration compared with standard high-flux hemodialysis when a high convection volume is delivered. Hemodiafiltration is also associated with improvements in other clinical outcomes, such as a reduction in intradialytic hypotension, and it is now used routinely to treat >100,000 patients, mainly in Europe and Japan.

Regulatory Considerations for Hemodiafiltration in the United States.

Online hemodiafiltration provides greater removal of higher molecular weight uremic retention solutes than conventional high-flux hemodialysis. However, online hemodiafiltration is used sparsely in the United States in part because of a paucity of delivery systems cleared for clinical use by the US Food and Drug Administration. Although a pathway for regulatory approval exists in the United States, concerns remain, particularly regarding online production of the large volumes of sterile, nonpyrogenic substitution fluid infused directly into the bloodstream to maintain fluid balance. Clearly defined testing protocols, acceptable to Food and Drug Administration, will be useful to show that an online hemodiafiltration system is capable of routinely achieving a sterility assurance level of 10-6 and nonpyrogenic levels of endotoxin. Large-scale clinical experience has shown that systems providing this level of performance when combined with certain design features, such as redundancy, and an appropriate quality management process can routinely and safely produce substitution fluid for online hemodiafiltration.

Agreement between 24-hour salt ingestion and sodium excretion in a controlled environment.

Accurately collected 24-hour urine collections are presumed to be valid for estimating salt intake in individuals. We performed 2 independent ultralong-term salt balance studies lasting 105 (4 men) and 205 (6 men) days in 10 men simulating a flight to Mars. We controlled dietary intake of all constituents for months at salt intakes of 12, 9, and 6 g/d and collected all urine. The subjects' daily menus consisted of 27 279 individual servings, of which 83.0% were completely consumed, 16.5% completely rejected, and 0.5% incompletely consumed. Urinary recovery of dietary salt was 92% of recorded intake, indicating long-term steady-state sodium balance in both studies. Even at fixed salt intake, 24-hour urine collection for sodium excretion (UNaV) showed infradian rhythmicity. We defined a ±25 mmol deviation from the average difference between recorded sodium intake and UNaV as the prediction interval to accurately classify a 3-g difference in salt intake. Because of the biological variability in UNaV, only every other daily urine sample correctly classified a 3-g difference in salt intake (49%). By increasing the observations to 3 consecutive 24-hour collections and sodium intakes, classification accuracy improved to 75%. Collecting seven 24-hour urines and sodium intake samples improved classification accuracy to 92%. We conclude that single 24-hour urine collections at intakes ranging from 6 to 12 g salt per day were not suitable to detect a 3-g difference in individual salt intake. Repeated measurements of 24-hour UNaV improve precision. This knowledge could be relevant to patient care and the conduct of intervention trials.

Bioinspired multiple-interaction model revealed in adsorption of low-density lipoprotein to surface containing saccharide and alkanesulfonate.

A new "multiple-interaction model" for low-density lipoprotein (LDL) adsorption to a specific surface containing saccharide and alkanesulfonate ligands is proposed. The model suggests that there are interactions of the saccharide component beyond electrostatic interactions of the alkanesulfonate component that both influence the LDL adsorption process. This concept of multiple interactions between saccharide and LDL was inspired by the similarity in structures of LDL receptors (LDLR), heparin, and heparans used in LDL-apheresis. The model was confirmed by SPR analysis by the adsorption maxima on SAM surfaces with different compositions of saccharide and alkanesulfonate and additionally by CD detection of the conformation of LDL when in contact with saccharide.

Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance.

The steady-state concept of Na(+) homeostasis, based on short-term investigations of responses to high salt intake, maintains that dietary Na(+) is rapidly eliminated into urine, thereby achieving constant total-body Na(+) and water content. We introduced the reverse experimental approach by fixing salt intake of men participating in space flight simulations at 12 g, 9 g, and 6 g/day for months and tested for the predicted constancy in urinary excretion and total-body Na(+) content. At constant salt intake, daily Na(+) excretion exhibited aldosterone-dependent, weekly (circaseptan) rhythms, resulting in periodic Na(+) storage. Changes in total-body Na(+) (±200-400 mmol) exhibited longer infradian rhythm periods (about monthly and longer period lengths) without parallel changes in body weight and extracellular water and were directly related to urinary aldosterone excretion and inversely to urinary cortisol, suggesting rhythmic hormonal control. Our findings define rhythmic Na(+) excretory and retention patterns independent of blood pressure or body water, which occur independent of salt intake.

Biomaterials in medical devices: an interview with Jörg Vienken of Fresenius Medical Care, Germany.

Biomaterial and biopolymer research have significant impact on the development as well as application of biotechnology. Biotechnology Journal recently attended the "Nanomaterials for Biomedical Technologies 2012" conference. We were privileged to have the opportunity to ask Prof. Dr. Jörg Vienken, VP of BioSciences at Fresenius Medical Care, a few questions relating to medical devices, the importance of publishing for industry, and also his advice for young scientists/engineers looking for a career in industry.

Contribution of polysulfone membranes to the success of convective dialysis therapies.

The majority of patients with chronic kidney disease are currently treated with dialyzers containing synthetic membranes. Of all the dialysis membranes made from these polymers, 93% are from the parent polyarylsulfone family of which 71% are from polysulfone (PSu) and 22% from polyethersulfone. The preference of nephrologists for PSu dialyzers signifies their versatility in terms of meeting the solute and fluid removal demands for all treatment modalities (low-and high-flux dialysis, online hemodiafiltration, hemofiltration). The unprecedented success and widespread usage of PSu membranes is attributed, in addition to efficient removal of a broad spectrum of uremic toxins, to other criteria required of modern dialysis therapies. Namely, effective endotoxin retention capacity, pronounced intrinsic biocompatibility and low cytotoxicity are factors which all contribute to minimal adverse clinical sequelae. Furthermore, PSu by virtue of its high thermal stability can be sterilized with steam, the preferred mode of sterilization as it does not have the disadvantages associated with other sterilization methods. However, there are significant differences between membranes made from PSu due to differences in membrane polymer recipes and manufacturing technologies. Although PSu may be the main constituent, these membranes are blended with other polymers, e.g. hydrophilizing agents, such as polyvinylpyrrolidone to give each membrane its characteristic profile. The relative amounts of the two (or more) co-polymers as well as the spinning conditions provide a fingerprint of each membrane in terms of solute separation characteristics, biocompatibility, cytotoxicity or endotoxin retention capabilities. PSu membrane-based dialyzers thus fulfill the crucial therapy requirements of current treatment modalities to varying extents. Thereby, different effects towards patient outcomes and treatment safety are achieved.

Covalent heparin modification of a polysulfone flat sheet membrane for selective removal of low-density lipoproteins: a simple and versatile method.

A simple, convenient and economical method for the heparinization of PSf membranes is described, with the aim of preparing an LDL adsorber for simultaneous LDL apheresis and hemodialysis. An atmospheric pressure glow discharge generator is used to activate the PSf membrane surface, with subsequent chemical binding of heparin in the presence of EDC and NHS. ATR-FTIR spectroscopy and XPS measurements confirm successful surface modification. The PSf-Hep membrane shows good blood compatibility, with a relatively low amount and normal morphology of adherent platelets. ELISA results indicate that the PSf-Hep membrane exhibits excellent selective affinity for LDL in single and binary protein solutions, suggesting potential applications in hemodialysis with simultaneous LDL removal.

Blood compatibility and permeability of heparin-modified polysulfone as potential membrane for simultaneous hemodialysis and LDL removal.

Heparin was covalently immobilized on PSf membranes to obtain a dialysis membrane with high affinity for LDL. WCA and streaming potential measurements were performed to investigate wettability and surface charge of the membranes. The morphology of the membranes was investigated by SEM. An ELISA was used to measure the adsorption and desorption of LDL on plain and modified PSf. Blood compatibility was studied by measurement of thrombin time, partial thromboplastin time, kallikrein activity and platelet adhesion. It was found that the blood compatibility of the membrane was improved by covalent immobilization of heparin at its surface. However, PSf-Hep membrane showed higher flux recovery after BSA solution filtration, which revealed antifouling property of PSf-Hep membranes.